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Future COVID-19 vaccines may need to be given annually, like the influenza vaccine, but carefully designed to avoid “immune imprinting” to prevent reduced efficacy against new variants.

Immune imprinting is a phenomenon whereby prior exposure to one virus strain limits the development of immunity against new variant strains of the virus, while mainly only boosting responses to the original strain.

The perspective, published in Trends in Immunology, was led by University of Melbourne Professor Stephen Kent, a laboratory head at the Doherty Institute, discusses whether new generation vaccines may need to be reformulated to combat a future global surge in infections.

“We need to adapt quickly to these different strains and include the components in the new vaccines that are different to the original strain,” Professor Kent said.

“We believe immune imprinting is going to be a problem and it is likely to be a growing issue every year when there is a new strain – that’s why we need to be thinking about the solution now. The good news is we are working towards a solution.”

Professor Kent said imprinting had already been widely studied in Influenza infections and that the immune response became “imprinted” against previous strains, limiting robust neutralising antibodies to new strains. Imprinting is one reason why the annual flu vaccine is only partially effective.

“We hypothesise that updated vaccines against SARS-CoV-2 variants might primarily boost “imprinted” immune responses to conserved regions of the spike protein to the detriment of new neutralising responses to new variants,” Professor Kent said.

“We argue that this “updated strain” vaccine strategy will still yield partial efficacy against the new variants, particularly for vaccines that induce potent neutralising responses.

“While existing vaccines have done a great job protecting us from the original SARS-CoV-2 infection, it is likely that new strains such as Delta will continue to emerge. In this case, repeated vaccine updates will be needed, and we should take into account the possibility that imprinting may limit vaccine effectiveness in the future.”

Professor Kent said large studies of booster vaccines are needed and that internationally these trials are expected to start reporting early next year. Research teams at the Doherty Institute, including Professor Kent’s, are working on vaccines against Delta and other variants that try to avoid reduced effectiveness from immune imprinting.

The team included many other members of the Doherty Institute including Dr Adam Wheatley, Dr Jennifer Juno, Dr Annette Fox, Professor Kanta Subbarao, and Dr Hyon-Xhi Tan.

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